Vertebrate corneas become transparent by a mechanism which remains unelucidated. Transparency does not arise coincident with the beginning of keratan sulfate biosynthesis, as was once thought. However, the apparent degree of sulfation of keratan sulfate and other glycosaminoglycans increases as transparency appears. Nevertheless, the specific activities of glycosaminoglycan sulfotransferases in the cornea remain reasonably constant during development. Thus, if the degree of sulfation of glycosaminoglycans controls corneal transparency to some degree, it may be regulated by the availability of the sulfate donor (PAPS), by extracellular sulfotransferases, or by both. Proposed research will test these hypotheses. Using a combination of immunological and biochemical techniques, including GLC/mass spectroscopy and ion-selective microelectrodes, we propose to study: 1) differentiation of corneal fibroblasts from the neural crest and their fibroblast populations in the eye; 2) control of glycosaminoglycan and glycoprotein biosynthesis in the developing cornea; 3) regulation of collagen biosynthesis by corneal cell-types; 4) role of the extracellular matrix in the development and maintenance of corneal transparency; and 5) role of extracellular materials in controlling the invasiveness of presumptive corneal fibroblasts and corneal nerves.